Anti-ILT7 antibody

Abstract

An antibody binding to IPC was obtained by using an animal cell in which a cell membrane protein associatable with ILT7 was co-expressed as an immunogen. The antibody of the invention has a high specificity which allows immunological distinction between other ILT family molecules and ILT7. The anti-ILT7 antibody of the invention bound to IPC and inhibited the activity thereof. With the anti-ILT7 antibody of the invention, the IPC activity can be inhibited and an interferon-related disease can be treated or prevented. ILT7 expression is maintained even in IPC in the presence of IFNα. Therefore, an inhibitory action of IPC activity by the anti-ILT7 antibody can be expected even in an autoimmune disease patient with an increased production of IFNα.

1. An isolated monoclonal antibody or an antigen binding fragment thereof which binds to an extracellular domain of human ILT7, wherein the monoclonal antibody or antibody fragment comprises the amino acid sequences according to any of the following i) to iii) as CDR1, CDR2, and CDR3 in the heavy chain variable region and the light chain variable region:
 CDR1 of a heavy chain variable region: SDYAWN (SEQ ID NO: 58); 
 CDR2 of a heavy chain variable region: YISYSGSTSYNPSLKSR (SEQ ID NO: 59); and 
 CDR3 of a heavy chain variable region: SPPYYAMDY (SEQ ID NO: 60); 
 CDR1 of light chain variable region: KASQDVGTAVA (SEQ ID NO: 61): 
 CDR2 of a light chain variable region: WASTRIAT (SEQ ID NO: 62); and 
 CDR3 of a light chain variable region: QQYSSYPLT (SEQ ID NO: 63); 
 ii) CDR1 of a heavy chain variable region: SYWIH (SEQ ID NO: 64); 
 CDR2 of a heavy chain variable region: RIYPGTGSTYNNEKFKG (SEQ ID NO: 65); and 
 CDR3 of a heavy chain variable region: YPTYDWYFDV (SEQ ID NO: 66): 
 CDR1 of a light chain variable region: RASQSISNYLH (SEQ ID NO: 67); 
 CDR2 of a light chain variable region: YASQSIS (SEQ ID NO: 68); and 
 CDR3 of a light chain variable region: QQSNSWPLT (SEQ ID NO: 69); 
 iii) CDR1 of a heavy chain variable region: SDYAWN (SEQ ID NO: 70); 
 CDR2 of a heavy chain variable region: YISYSGSTSYNPSLKSR (SEQ ID NO: 71); 
 CDR3 of a heavy chain variable region: ALPLPWFAY (SEQ ID NO: 72); 
 CDR1 of a light chain able region: KASQDVGTAVA (SEQ ID NO: 73); 
 CDR2 of a light chain variable region: WASTRHT (SEQ ID NO: 74); and 
 CDR3 of a light chain variable region: QQYSSYPYT (SEQ ID NO: 75). 
 
     
     
       2. The monoclonal antibody or the antibody fragment according to  claim 1 , wherein the monoclonal antibody or antibody fragment binds to a human interferon producing cell. 
     
     
       3. A hybridoma which produces either of the monoclonal antibodies according to  claim 1  or  2 . 
     
     
       4. The monoclonal antibody or the antibody fragment according to  claim 1 , wherein the monoclonal antibody or antibody fragment comprises the mature sequences of the amino acid sequences selected from any of the following combinations (a) to (c) as the heavy chain variable region and the light chain variable region:
 a) a heavy chain variable region of SEQ ID NO: 39 and a light chain variable region of SEQ ID NO: 41; 
 b) a heavy chain variable region of SEQ ID NO: 43 and a light chain variable region of SEQ ID NO: 45; and 
 c) a heavy chain variable region of SEQ ID NO: 47 and a light chain variable region of SEQ ID NO: 49. 
 
     
     
       5. A monoclonal antibody or an antibody fragment, according to  claim 1 , capable of recognizing human ILT7 which can be obtained by the following steps of:
 (1) administering to an immune animal a cell which exogenously expresses a protein comprising an extracellular domain of human ILT7 and a molecule Which associates with human ILT7; 
 (2) selecting an antibody producing cell which produces the antibody which binds to human ILT7 from the antibody producing cell of the immune animal; and 
 (3) culturing the antibody producing cell selected by step (2) and recovering an antibody capable of recognizing human ILT7 from the culture. 
 
     
     
       6. An inhibitor for the activity of an interferon producing cell comprising a monoclonal antibody or antibody fragment according to  claim 1 , which binds to human ILT7 and inhibits the activity of an interferon producing cell. 
     
     
       7. The inhibitor for the activity of an interferon producing cell according to  claim 6 , wherein the activity of the interferon producing cell is due to either the interferon producing activity or the survival of the interferon producing cell, or both of them. 
     
     
       8. A reagent for detecting an interferon producing cell comprising a monoclonal antibody or an antibody fragment, according to  claim 1 , which binds to an extracellular domain of human ILT7. 
     
     
       9. A method for detecting an interferon producing cell, comprising the steps of: contacting a test cell with the monoclonal antibody or the antibody fragment of  claim 1 ; and detecting the monoclonal antibody or the antibody fragment which is bound to the cell. 
     
     
       10. A method for inhibiting the activity of an interferon producing cell comprising a step of contacting an interferon producing cell with the monoclonal antibody or antibody fragment according to  claim 1 . 
     
     
       11. A method for inhibiting the activity of an interferon producing cell in a human patient comprising a step of administering the monoclonal antibody or antibody fragment according to  claim 1  to a human patient. 
     
     
       12. The method according to a  claim 10  or  11 , wherein the activity of the interferon producing cell is due to either the interferon producing activity or the survival of the interferon producing cell, or both of them. 
     
     
       13. A monoclonal antibody which is produced by a hybridoma ILT7#11 deposited at the International Patent Organism Depositary under Accession number FERM BP-10704 or a hybridoma ILT7#17 deposited at the International Patent Organism Depositary under Accession number FERM BP-10705, or a fragment comprising its antigen binding region. 
     
     
       14. A hybridoma ILT7#11 deposited at the International Patent Organism Depositary under Accession number FERM BP-1O704 or a hybridoma ILT7#17 deposited at the International Patent Organism Depositary under Accession number FERM BP-10705. 
     
     
       15. A method for producing a monoclonal antibody, comprising the steps of: culturing the hybridoma according to  claim 14 ; and collecting the monoclonal antibody from the culture.